Expressions Of HTERT And E2F-1 Proteins In Colorectal Carcinoma Tissues And Their Clinical Significance

Objective: The main objective of this study was to analysis the alteration of colorectal carcinoma(CRC) clinical pathological characteristics in Qingyuan district over the past twenty years, and explored the relationship between prognosis and human telomerase reverse transcriptase(hTERT) and transcription factor E2F-1 expressions in colorectal carcinoma tissues.Methods: 1. The clinical pathology of 1087 CRC cases were analysised in Qingyuan district over the past twenty years(from 1995 to 2014). The alterations of CRC clinical pathological characteristics between 1995-2004 and 2005-2014 were observed.2. 134 cases of CRC, 74 cases of colorectal adenomas(CRA) and 28 cases of normal colorectal mucosa(NCRM) were selected which diagnosed between December 2005 and April 2008, the expressions of hTERT and E2F-1 protein in those tissues were detected by tissues microarray and immunohistochemical assay.3. Routine follow-up were performed in 134 CRC cases. The relationship between the expressions of hTERT and E2F-1 protein and the CRC clinical pathological characteristics and prognosis were also explored.Results: 1. The clinical pathologic characteristics and their alteration in 1087 CRC cases1.1 The clinical pathologic characteristics in 1087 CRC cases(1) The male and female ratios in 1087 CRC cases was 1.28:1, the median age of these cases was 62, predilection location of these cases were listed as follows: rectum(43.4%), ascending colon(20.9%), sigmoid colon(18.6%), descending colon(8.6%), transverse colon(5.2%), cecum(3.4%).(2) The proportion of liver metastasis rate in male group were higher than that in female group(P<0.05); there was no significant difference between the two groups in terms of age, location, histological grade, lymphatic metastasis and Dukes stage(P>0.05).(3) The incidence rate of high grade tumor and lymphatic metastasis, as well as proportion of Duke C and D stage in younger age-group(age ?40 years old) were higher than those in older age-group(age > 40 years old) in CRC patients(P<0.05); there was no significant difference between the two groups in terms of sex, location and liver metastasis rate(P>0.05).(4) The incidence rate of high grade tumor for colon carcinoma patients were higher than that for rectum carcinoma patients(P<0.05); There was no significant difference between the two groups in terms of sex, age, lymphatic metastasis and liver metastasis rate(P>0.05).1.2. The alteration of CRC clinical pathological characteristics over the past twenty years(1) The median age for CRC patients between 2005 and 2014(62 years old) was higher than that between 1995 and 2004(60 years old). The proportion of tumors occured in older age-group(age > 40 years old) for CRC patients between 2005 and 2014(92.4%) was higher than that between 1995 and 2004(85.0%)(P<0.05); The proportion of tumors occured in rectal for CRC patients between 2005 and 2014(45.3%) was higher than that between 1995 and 2004(38.1%)(P<0.05).(2) There was no significant difference in the male and female ratios, histological grade, lymphatic metastasis rate and Dukes' stage of CRC patients between lately group(between 2005 and 2014) and early group(between 1995 and 2004)(P>0.05).2. The expression and prognostic value of hTERT and E2F-1 protein in colorectal carcinoma tissues2.1 The expression of hTERT and E2F-1 protein in different colorectal tissuesThe positive expression rate of hTERT protein in 28 cases of NCRM, 74 cases of CRA, 134 cases of CRC tissues were 28.6%, 40.5% and 47.0%, respectively, showing a gradual increased trend during the carcinogenesis of CRC(P>0.05). The positive expression rate of E2F-1 protein in NCRM, CRA and CRC tissues were 100%, 95.9% and 72.4%, respectively, showing a gradual decreased trend during the carcinogenesis of CRC(P< 0.05)?2.2 The relationship between hTERT protein expression, E2F-1 protein expression and the CRC clinical pathological characteristicsThe expression of hTERT protein was related to the gender, Dukes stage and lymphatic metastasis of the CRC patients(P<0.05). The expression of E2F-1 protein was related to the Dukes stage and lymphatic metastasis of the CRC patients(P<0.05)3.3 The relationship between hTERT protein expression, E2F-1 protein expression and the CRC prognosis(1) Among a total of 134 CRC cases, there were 74 cases with complete follow-up data; the follow-up rate was 55.2%, the median survival time was 61 months, and the 5 year relative survival was 55.4%.(2) Kaplan-Meier survival analysis demonstrated that Dukes stage, lymphatic metastasis, the expressions of hTERT protein and E2F-1 protein were correlated with the overall survival time of CRC patients(P<0.05).(3) Multivariate analysis demonstrated that Dukes stage and the expression of hTERT protein were independent prognostic factors for CRC patients(P<0.05).(4) For patients with positive expression of hTERT protein, the survival rate of these patients in Dukes C and D stage after chemotherapy was higher than that without received any chemotherapy(P<0.05).Conclusion:1. The changes of age and location of CRC in recent years have a certain guiding significance for the region to develop CRC prevention strategies2. The expression of hTERT and E2F-1 protein were closely related with the progression and prognosis for CRC patients. E2F-1 may play a role in tumorigenesis of CRC. hTERT protein expression level detection may helpful to select chemotherapy regimen for post-operative CRC patients with Dukes C and D stage.